There are currently 15.7 million people or 5.9% of the population in the United States who suffer from diabetes mellitus. Each day approximately 2,200 people are diagnosed with diabetes and roughly 798,000 people will be diagnosed this year. Diabetes is the seventh leading cause of death (sixth-leading cause of death by disease) in the United States.
Diabetes mellitus, more commonly known as diabetes, is a disease in which the body does not produce and/or properly use insulin, a hormone that aids the body in converting sugars and other foods into energy. In a non-diabetic individual, insulin is produced in the pancreas at the islets of Langerhans in response to an increase of glucose in the gut and/or blood. Insulin then acts in conjunction with the liver to control glucose metabolism in the body. While diabetes is typically thought of as a blood-sugar disease, diabetes may result in numerous life-threatening complications. For example, diabetes may lead to various microvascular diseases, such as retinopathy, nephropathy, and neuropathy. In the United States, diabetes is the leading cause of new cases of blindness in people ages 20 to 74, is the leading cause of end-stage renal disease, and is the most frequent cause of lower limb amputations. Diabetic individuals also have a higher likelihood of developing life-threatening macrovascular diseases, such as heart disease and stroke.
Several types of diabetes exist. Insulin dependent diabetes mellitus (IDDM), commonly referred to as Type 1 diabetes, is an auto-immune disease that affects the islets of Langerhans, destroying the body's ability to produce insulin. Type 1 diabetes may affect as many as 1 million people in the United States. Non-insulin dependent diabetes mellitus (NIDDM), commonly referred to as Type 2 diabetes, is a metabolic disorder resulting from the body's inability to produce enough insulin or properly use the insulin produced. Roughly 90 percent of all diabetic individuals in the United States suffer from Type 2 diabetes, which is usually associated with obesity and a sedentary lifestyle.
In general, the goal of diabetes treatment is to control glucose level in the blood and maintain it in a range that mimics that of a non-diabetic individual, namely reproduces natural physiological glucose homeostasis. A recent study called the Diabetes Control and Complications Trial (DCCT) found that keeping blood sugar levels as close to normal as possible significantly reduced the damage to eyes, kidneys, and nerves caused by high blood sugar. The DCCT studied 1,400 Type 1 diabetics for an average of seven years to find out if significantly lowering blood glucose levels would reduce diabetic complications such as eye, nerve, or kidney disease. Half the study group continued their usual treatment plan, while the other half maintained extremely tight control over their blood sugar levels—attempting to keep those levels as close to those of nondiabetic people at all times.
Overall, people who exercised tight control over their blood sugar had significantly less damage to their eyes, kidneys, and nerves. For example, diabetic eye disease started in only one-quarter as many people, kidney disease started in only half as many people, nerve disease started in only one-third as many people, and far fewer people who already had early forms of these three complications got worse. In fact, the results were so striking that doctors ended the trial early in order to bring all patients over to the tight control treatment. Because of the significant decrease in diabetic complications, the American Diabetes Association recommends maintaining tight control over blood sugar levels in all Type 1 diabetics. However, tight control treatment utilizing conventional injectable insulin therapies may present risks that outweigh these benefits for some patients.
The DCCT reported that people in the tight control group had triple the normal risk of low blood sugar (hypoglycemic) episodes. The brain relies exclusively on glucose for energy, so extremely low blood sugar levels can result in tiredness, headache, confusion, or even unconsciousness. This increased risk of hypoglycemic episodes may have prompted the American Diabetes Association to recommend that certain individuals refrain from attempting to maintain a tight control regimen, despite the long-term benefits that tight control treatment may provide. For example, children should not be put on a program of tight control because having enough glucose in the blood is vital to brain development. As another example, elderly people probably should not go on tight control. Hypoglycemia can cause strokes and heart attacks in older people. As yet another example, some people who already have complications associated with diabetes mellitus should not be on tight control. As still other examples, people with end-stage kidney disease or severe vision loss probably should not attempt to achieve tight control. Some people who have coronary artery disease or vascular disease probably should not try tight control. As yet another example, people who often have low blood glucose reactions probably should not go on tight control. Thus, the increased risk of hypoglycemia when utilizing a conventional injection therapy regimen to maintain tight control of blood glucose may prevent many people, who would otherwise benefit from such a regimen, from pursuing this course of treatment.
The increased risk of hypoglycemia may make maintaining tight regulation using conventional injectable insulin therapies a time consuming endeavor. To achieve tight control utilizing conventional injectable insulin therapies, individuals suffering from diabetes must pay more attention to their diet and exercise. They must measure their blood glucose levels more often. They must provide themselves with a low level of insulin at all times and take extra insulin when they eat. The American Diabetes Association recommends two conventional ways of providing a more natural level of insulin: multiple daily injection therapy and an insulin pump. In multiple daily injection therapy, the diabetic patient takes three or more insulin shots per day—usually a shot of short-acting or regular insulin before each meal and a shot of intermediate- or long-acting insulin at bedtime. With an insulin pump, the diabetic patient wears a tiny pump that releases insulin into his or her body through a plastic tube. The pump usually gives a constant small dose of short-acting or Regular insulin, and may be manipulated to release extra insulin when needed, such as before a meal. With either method, the diabetic patient should test his or her blood glucose levels several times a day, for example before each shot or extra dose of insulin to know how many units to take and how long before eating to take them, two or three hours after eating to make sure he or she took enough insulin, and before driving.
The increased risk of hypoglycemia may make pursuing a tight regulation regimen that utilizes conventional injection therapies a costly course of treatment. Ensuring an acceptable risk of hypoglycemia may involve employing a health care team that includes a doctor, a dietitian, a diabetes educator, a mental health professional, and other health care professionals, who may need to spend a lot of time with the patient to determine the precise timing and doses of insulin needed and the lifestyle changes needed to maintain tight control using conventional insulin injection therapies without undue risk of hypoglycemia. The diabetic patient may even need to stay in the hospital for a few days so that the health care team can monitor blood glucose and be close at hand in the event any hypoglycemic episodes are experienced by the patient as the tight control regimen is determined. Even after determining the regimen, the monitoring costs of maintaining the regimen may be quite high.
In view of the foregoing, there is a need in the art for methods of treating diabetes mellitus that provide a reduced risk of hypoglycemic episodes.